Trypsin is a digestive enzyme synthesized by the pancreas which acts as a serine protease. The mechanism by which this occurs involves the hydrolysis of peptide bonds using the chemical properties of Histidine, Aspartic Acid, and Serine, which are all polar amino acids. When these amino acids are combined in the trypsin actives-site, they form a catalytic triad, which is a charge relay that interacts with the serine active site and increases the nucleophilic interaction between the enzyme and substrate. The trypsin enzyme also possesses an oxyanion hole in the center of the molecule. This hole is formed by the amide backbone of the Gly- 193 and the Ser-195 amino acids. This oxyanion hole stabalizes the negative charge that is on the carbonyl oxygen throughout the hydrolysis of the peptide. The specificity of this enzyme comes from the Asp-189 residue that is found in the catalytic pocket. This aspartate's negative charge is responsible for the attraction and stabilization of positively charged amino acids. This means that the enzyme usually attaches and cleaves the proteins at the C terminus. This results in a thermodynamically favorable reaction, allowing the hydrolysis of the peptide bonds to occur. In order to initiate the attack, the group activates the serine group through base catalysis. This forms a tetrahedral intermediate which is immediately altered by acid catalysis of the NH2, resulting in a broken peptide bond within the substrate polypeptide. Once the peptide bond has been broken and the enzyme-substrate complex has been formed, a bond forms between the water molecule and the carbonyl group of the enzyme-substrate complex. Finally, one of the carbon-oxygen bond breaks and the enzyme is reproduced as a side product of the peptide hydrolysis.
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References
- ↑ Radisky ES, Lee JM, Lu CJ, Koshland DE Jr. Insights into the serine protease mechanism from atomic resolution structures of trypsin reaction intermediates. Proc Natl Acad Sci U S A. 2006 May 2;103(18):6835-40. Epub 2006 Apr 24. PMID:16636277
